Clinical and Kinematic Features of Valproate-Induced Tremor and Differences with Essential Tremor.

Tremor is a common movement disorder that can be induced by medications, including valproate, which is used for the treatment of epilepsy. However, the clinical and neurophysiological features of valproate-induced tremor are still under-investigated. We performed a clinical and kinematic assessment of valproate-induced tremor by considering tremor body distribution and activation conditions. We investigated possible correlations between demographic and clinical data and kinematic features. Valproate-induced tremor results were also compared with those collected in a large sample of patients with essential tremor. Sixteen valproate-induced tremor patients and 93 essential tremor patients were enrolled. All participants underwent a standardised neurological examination and video recording. Patients also underwent an objective assessment of postural, kinetic and rest tremor of the upper limbs and head tremor through kinematic analysis. Nonparametric tests were used for statistical comparisons between the two groups. Clinical evaluation showed a higher occurrence of rest tremor as well as head or voice, and lower limb involvement in patients with valproate-induced tremor. Kinematic analysis showed a substantial variability in the tremor features of patients with valproate-induced tremor. Compared to essential tremor, we found a higher occurrence of rest tremor of the upper limbs and the involvement of more body segments in valproate-induced tremor patients. Valproate-induced tremor has distinctive clinical and kinematic features, which may suggest that valproate interferes with the cerebellar functions.

Functional gait disorders, clinical phenomenology, and classification.

BACKGROUND: Functional gait disorders (FGDs) are relatively common in patients presenting for evaluation of a functional movement disorder (FMD). The diagnosis and classification of FGDs is complex because patients may have a primary FGD or a FMD interfering with gait. METHODS: We performed a detailed evaluation of clinical information and video recordings of gait in patients diagnosed with FMDs. RESULTS: We studied a total of 153 patients with FMDs, 68% females, with a mean age at onset of 36.4 years. A primary FGD was observed in 39.2% of patients; among these patients, 13 (8.5%) had an isolated FGD (a gait disorder without other FMDs). FMDs presented in 34% of patients with otherwise normal gait. Tremor was the most common FMD appearing during gait, but dystonia was the most common FMD interfering with gait. Patients with FGD had a higher frequency of slow-hesitant gait, astasia-abasia, bouncing, wide-based gait and scissoring compared with patients with FMDs occurring during gait. Bouncing gait with knee buckling was more frequently observed in patients with isolated FGD (P = 0.017). Patients with FGDs had a trend for higher frequency of wheelchair dependency (P = 0.073) than those with FMDs interfering with gait. CONCLUSIONS: Abnormal gait may be observed as a primary FGD or in patients with other FMDs appearing during gait; both conditions are common and may cause disability.

Tremor.

INTRODUCTION OR BACKGROUND: Tremor is one of the commonest movement disorders and can be disabling. There are many causes and treatment options include medications, adaptations, botulinum toxin injections and functional neurosurgery. SOURCES OF DATA: Pubmed.gov peer-reviewed journal articles and reviews. AREAS OF AGREEMENT: A new tremor classification has been published. Axis 1 of this classification highlights the clinical characteristics of tremor and axis 2 is dedicated to aetiology. The cerebello-thalamo-cortical network and connections to other brain areas is emerging as pivotal to many types of tremor. AREAS OF CONTROVERSY: There has been ongoing debate around the clinical entity of essential tremor and its pathophysiological basis. GROWING POINTS: Increasing understanding of the pathophysiology underpinning tremor is helping to improve classification and is pushing forward trials of new treatment options, particularly surgical options. AREAS TIMELY FOR DEVELOPING RESEARCH: With deeper phenotyping from the new classification, genetics of common forms of tremor are ripe for discovery. New pharmacological therapeutic options are needed to complement the better understanding of the basis of tremor.

Contrast and Homogeneity Feature Analysis for Classifying Tremor Levels in Parkinson's Disease Patients.

Early detection of different levels of tremors helps to obtain a more accurate diagnosis of Parkinson's disease and to increase the therapy options for a better quality of life for patients. This work proposes a non-invasive strategy to measure the severity of tremors with the aim of diagnosing one of the first three levels of Parkinson's disease by the Unified Parkinson's Disease Rating Scale (UPDRS). A tremor being an involuntary motion that mainly appears in the hands; the dataset is acquired using a leap motion controller that measures 3D coordinates of each finger and the palmar region. Texture features are computed using sum and difference of histograms (SDH) to characterize the dataset, varying the window size; however, only the most fundamental elements are used in the classification stage. A machine learning classifier provides the final classification results of the tremor level. The effectiveness of our approach is obtained by a set of performance metrics, which are also used to show a comparison between different proposed designs.

Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society.

BACKGROUND: Consensus criteria for classifying tremor disorders were published by the International Parkinson and Movement Disorder Society in 1998. Subsequent advances with regard to essential tremor, tremor associated with dystonia, and other monosymptomatic and indeterminate tremors make a significant revision necessary. OBJECTIVES: Convene an international panel of experienced investigators to review the definition and classification of tremor. METHODS: Computerized MEDLINE searches in January 2013 and 2015 were conducted using a combination of text words and MeSH terms: "tremor", "tremor disorders", "essential tremor", "dystonic tremor", and "classification" limited to human studies. Agreement was obtained using consensus development methodology during four in-person meetings, two teleconferences, and numerous manuscript reviews. RESULTS: Tremor is defined as an involuntary, rhythmic, oscillatory movement of a body part and is classified along two axes: Axis 1-clinical characteristics, including historical features (age at onset, family history, and temporal evolution), tremor characteristics (body distribution, activation condition), associated signs (systemic, neurological), and laboratory tests (electrophysiology, imaging); and Axis 2-etiology (acquired, genetic, or idiopathic). Tremor syndromes, consisting of either isolated tremor or tremor combined with other clinical features, are defined within Axis 1. This classification scheme retains the currently accepted tremor syndromes, including essential tremor, and provides a framework for defining new syndromes. CONCLUSIONS: This approach should be particularly useful in elucidating isolated tremor syndromes and syndromes consisting of tremor and other signs of uncertain significance. Consistently defined Axis 1 syndromes are needed to facilitate the elucidation of specific etiologies in Axis 2. © 2017 International Parkinson and Movement Disorder Society.

[Rare tremor syndromes]. / Seltene Tremorsyndrome.

BACKGROUND: There is a group of uncommon sporadic tremor syndromes, which are only partially taken into account in the current classification of tremor. Their knowledge is of diagnostic and therapeutic relevance and they should be considered in the differential diagnosis of frequent tremor syndromes. OBJECTIVE: Differential diagnostics and treatment of uncommon tremor syndromes. METHOD: Literature search (PubMed, Google Scholar). RESULTS: Holmes tremor, myorhythmia, palatal tremor, limb-shaking transient ischemic attack (TIA), tardive tremor, neuropathic tremor, tremor induced by peripheral trauma and orthostatic tremor syndrome are described. CONCLUSION: Uncommon sporadic tremor syndromes are mainly symptomatic with various underlying neurological or systemic pathologies. Their recognition accelerates the diagnostic process and has therapeutic relevance.

[Genetics of tremor]. / Genetik des Tremors.

BACKGROUND: Tremor is a symptom of many diseases and can constitute a disease of its own: essential tremor. OBJECTIVE: The genetics of essential tremor and differential diagnosis of monogenic diseases with the symptom tremor. MATERIAL AND METHODS: Literature search and search of clinical genetics databases, e.g. OMIM, GeneReviews, MDSGene and the German Neurological Society (DGN) guidelines. RESULTS: The genetics of essential tremor remain unresolved in spite of large, adequately powered studies. Tremor is a symptom of differential diagnostic value in many movement disorders. A slight tremor might have been missed or not reported in many descriptions of movement disorders. CONCLUSION: Progress in the genetics of essential tremor probably requires a more detailed phenotyping allowing stratification into phenotypically defined subgroups. Tremor should always be included in the examination and description of movement disorders even if tremor is not a cardinal symptom. Tremor might be helpful in the differential diagnosis of hereditary dystonia, hereditary ataxia, spastic paraplegia and other movement disorders.

[The new tremor classification of the International Parkinson and Movement Disorder Society : Update on frequent tremors]. / Die neue Tremorklassifikation der International Parkinson and Movement Disorder Society : Update zu häufigen Tremores.

Tremor is one of the most frequent movement disorders. The recently published new classification of the Movement Disorder Society separates the clinical description of tremor syndromes as so-called axis 1 symptom constellations from the etiologies of tremor (axis 2). The same tremor syndromes can therefore be combined with different causes and vice versa. The terminology used in this classification is precisely defined and thereby also the necessary language for medical communication. Frequent tremor syndromes, such as enhanced physiologic tremor, dystonic and parkinsonian tremor as well as focal tremors and task and position-specific tremors are discussed with respect to the phenomenology, and current therapy.

Relationship between the plasma levels of neurodegenerative proteins and motor subtypes of Parkinson's disease.

The aim of our study is to examine the plasma levels of the four kinds of neurodegenerative proteins in plasma: α-syn, T-tau, P-tau181, and Aß-42 in Parkinson's disease (PD) and to evaluate the relationship between their plasma levels and PD motor subtypes. 84 patients with PD were enrolled in our study, and finally, 73 of them were classified into the tremor-dominant subtype (TD) and the postural instability gait difficulty subtype (PIGD). Their motor performance was evaluated by a series of clinical assessments: Freezing of Gait Questionnaire (FOGQ), Timed Up and Go (TUGs), Tinetti balance, and Tinetti gait. Plasma levels of these proteins were measured by enzyme-linked immunosorbent assay (ELISA). The plasma level of α-syn was significantly higher in PD patients when compared to controls (p = 0.004), and significantly higher in the PIGD group when compared to the TD group (p = 0.03). While the plasma level of Aß-42 was significantly lower in PD patients than in controls (p = 0.002), and significantly lower in the PIGD group than in the TD group (p = 0.05). In PD patients, the plasma level of α-syn (r = -0.355, p < 0.001) was significantly related to the severity of Tenitti Gait score, even after performing multiple linear regression (p = 0.002). While the plasma level of Aß-42 (r = -0.261, p < 0.05) was significantly associated with the severity of PIGD score and remained correlate when performed multiple linear regression (p = 0.005). The patients with PIGD subtype are characterized with a lower level of plasma Aß-42 and a higher plasma level of α-syn, which may be used as biomarkers for diagnosis and progression of the subtypes of PD.

Unusual tremor syndromes: know in order to recognise.

Tremor is a common neurological condition in clinical practice; yet, few syndromes are widely recognised and discussed in the literature. As a result, there is an overdiagnosis of well-known causes, such as essential tremor. Many important unusual syndromes should be considered in the differential diagnosis of patients with tremor. The objective of this review is to provide broad clinical information to aid in the recognition and treatment of various unusual tremor syndromes in the adult and paediatric populations. The review comprised of a comprehensive online search using PubMed, Ovid database and Google Scholar to identify the available literature for each unusual tremor syndrome. The review includes fragile X-associated tremor/ataxia syndrome, spinocerebellar ataxia type 12, tremors caused by autosomal recessive cerebellar ataxias, myorhythmia, isolated tongue tremor, Wilson's disease, slow orthostatic tremor, peripheral trauma-induced tremor, tardive tremor and rabbit syndrome, paroxysmal tremors (hereditary chin tremor, bilateral high-frequency synchronous discharges, head tremor, limb-shaking transient ischaemic attack), bobble-head doll syndrome, spasmus nutans and shuddering attacks. Rare tremors generally present with an action tremor and a variable combination of postural and kinetic components with resting tremors less frequently seen. The phenomenology of myorhythmia is still vague and a clinical definition is proposed. The recognition of these entities should facilitate the correct diagnosis and guide the physician to a prompt intervention.

Tremor entities and their classification: an update.

PURPOSE OF REVIEW: This review focuses on important new findings in the field of tremor and illustrates the consequences for the current definition and classification of tremor. RECENT FINDINGS: Since 1998 when the consensus criteria for tremor were proposed, new variants of tremors and new diagnostic methods were discovered that have changed particularly the concepts of essential tremor and dystonic tremor. Accumulating evidence exists that essential tremor is not a single entity rather different conditions that share the common symptom action tremor without other major abnormalities. Tremor is a common feature in patients with adult-onset focal dystonia and may involve several different body parts and forms of tremor. Recent advances, in particular, in the field of genetics, suggest that dystonic tremor may even be present without overt dystonia. Monosymptomatic asymmetric rest and postural tremor has been further delineated, and apart from tremor-dominant Parkinson's disease, there are several rare conditions including rest and action tremor with normal dopamine transporter imaging (scans without evidence of dopaminergic deficit) and essential tremor with tremor at rest. SUMMARY: Increasing knowledge in the last decades changed the view on tremors and highlights several caveats in the current tremor classification. Given the ambiguous assignment between tremor phenomenology and tremor etiology, a more cautious definition of tremors on the basis of clinical assessment data is needed.

The heterogeneity of cognitive symptoms in Parkinson's disease: a meta-analysis.

Several studies have reported heterogeneity in cognitive symptoms associated with specific characteristics of patients with Parkinson's disease (PD). Indeed, researchers have characterised subtypes of patients suffering from PD according to various criteria. Those most frequently used are the type of predominant motor symptoms (tremors or non-tremor symptoms), age at onset and presence of depression. Some characteristics, like the predominant motor subtypes, as well as the presence of depression, are more widely used to categorise cognitive differences between patients. The goal of this study was to analyse the impact of the type of predominant motor symptoms and depression on cognition in PD. A meta-analysis of 27 studies (from 1989 to 2012) was carried out to calculate the average effect size of these factors on the most often used cognitive test during those past years to evaluate cognitive skills, the Mini-Mental State Examination. The studies analysed showed significant mean weighted effect sizes on cognition for the type of motor symptoms (d=0.42; 95% CI 0.30 to 0.54) and for depression (d=0.52; 95% CI 0.38 to 0.66). These results suggested that PD participants with non-tremor predominant motor symptoms or with depression had more or more severe cognitive impairments. Identification of different subtypes in PD is important for a better understanding of the cognitive symptoms associated with this disease. Better knowing the impact of different features of PD subgroups could help to design more appropriate treatments for patients with PD.

Prevalence and clinical classification of tremor in elderly--a community-based survey in Brazil.

Prevalence data on different types of tremor among the elderly population are very scarce. The objective of this study was to study the prevalence of tremor in a community-dwelling elderly population in the town of Bambuí, Brazil. The authors studied 1186 inhabitants aged≥64 years. This was a 2-phase study in which all participants who screened positive in a questionnaire for tremor and parkinsonism or who used drugs capable of causing/suppressing tremor were examined. In this population, the prevalence rate was 17.4% for tremor, 7.4% for essential tremor, 5.6% for parkinsonian tremor, 2.8% for enhanced physiological tremor, and 1.6% for other causes. There were no gender differences in prevalence rates for all types. Patients who had Parkinson's disease with tremor were older than those who had essential tremor, whereas patients who had enhanced physiological tremor were significantly younger. The age-specific prevalence of tremor increased with advancing age for both men and women. The prevalence of tremor in the studied population was high and increased with advancing age. Essential tremor, parkinsonian tremor, and enhanced physiological tremor were the most commonly identified causes. © 2013 Movement Disorder Society.

Tremor associated with focal and segmental dystonia.

BACKGROUND AND PURPOSE: Tremor occurs in 10-85% of patients with focal dystonia as so-called dystonic tremor or tremor associated with dystonia. The aim of this study was to assess the incidence and to characterize parameters of tremor accompanying focal and segmental dystonia. MATERIAL AND METHODS: One hundred and twenty-three patients with diagnosis of focal and segmental dystonia together with 51 healthy controls were included in the study. For each participant, clinical examination and objective assessment (accelerometer, electromyography, graphic tablet) of hand tremor was performed. Frequency and severity of tremor were assessed in three positions: at rest (rest tremor); with hands extended (postural tremor); during 'finger-to-nose' test and during Archimedes spiral drawing (kinetic tremor). Based on the mass load test, type of tremor was determined as essential tremor type or enhanced physiological type. RESULTS: The incidence of tremor was significantly higher in dystonic patients as compared to controls (p = 0.0001). In clinical examination, tremor was found in 50% of dystonic patients, and in instrumental assessment in an additional 10-20%. The most frequent type of tremor was postural and kinetic tremor with 7 Hz frequency and featured essential tremor type. In the control group, tremor was detected in about 10% of subjects as 9-Hz postural tremor of enhanced physiological tremor type. No differences were found between patients with different types of dystonia with respect to the tremor incidence, type and parameters (frequency and severity). No correlations between tremor severity and dystonia severity were found either.

An update on tremors.

PURPOSE OF REVIEW: This review describes the most recent advances in epidemiology, classification, genetics, pathology and treatment of essential tremor. In addition, recent advances in more rare forms of tremor are summarized. RECENT FINDINGS: Clinical, biochemical, pathological and imaging studies suggest an abnormal functioning of the cerebellum in essential tremor. Minor changes of cognition and personality may be due to secondary effects. Dementia and possible shortened life span seem to be limited to late-onset essential tremor. Many of these issues are not yet finally settled and need confirmation in further studies. The current essential tremor classification seems not to reflect the variety of phenotypic expressions. Regarding treatment, there is now a level B evidence for topiramate. Levetiracetam may induce a positive response in Holmes tremor, but is ineffective in orthostatic tremor. SUMMARY: These findings have extended our knowledge about essential tremor. It appears that a new, more distinct classification system is required. Recent treatments have remained unchanged.

The usefulness of accelerometric registration with assessment of tremor parameters and their symmetry in differential diagnosis of parkinsonian, essential and cerebellar tremor.

BACKGROUND AND PURPOSE: The aim of the study was to perform an analysis of the recorded tremor using accelerometry and select those parameters that are the most useful in differentiation of tremor types. MATERIAL AND METHODS: We examined 45 patients with parkinsonian tremor (PT), 39 patients with essential tremor (ET) and 35 patients with cerebellar tremor (CT). The control group consisted of 52 healthy persons. The analysis included tremor intensity, frequency of spectral peaks, centre frequency, standard deviation of the centre frequency, and harmonic index. Parameters of tremor were compared between particular groups of patients with pathological tremor and with the control group. The side-to-side symmetry of these parameters was also analysed. RESULTS: Tremor intensity was significantly higher in patients than in controls. There was a significant side-to-side asymmetry of intensity in all patient groups. Significantly lower peak frequency, centre frequency and standard deviation of centre frequency were found in patients compared to the control group. The frequency was symmetric in ET and in controls, but asymmetric in other subjects. The differences between hands regarding the standard deviation of centre frequency were significantly greater in all patient groups than in controls, who revealed no difference of this parameter between sides. Harmonic index was significantly greater and asymmetric in all groups of patients when compared to the control group. CONCLUSIONS: Standard deviation of centre frequency and harmonic index are the most valuable variables in differentiation of tremor. The assessment of symmetry of tremor parameters is useful in discrimination of various types of pathological tremor.

Tremor--some controversial aspects.

The commonest cause of pathological tremor is essential tremor (ET). However, it has proved difficult to identify genetic mutations causing ET, particularly because other causes of tremor continue to be misdiagnosed as ET. Whether subjects with dystonia or Parkinson's disease (PD) carry an increased genetic risk of developing ET, or vice versa, is controversial. In addition, the notion of a separate disorder of benign tremulous parkinsonism (BTP) has been debated. This article gives a selective viewpoint on some areas of uncertainty and controversy in tremor.

A practical guide to the differential diagnosis of tremor.

Tremor is, by definition, a rhythmic oscillation of a body part. It is the most prevalent movement disorder in clinical medicine, so doctors working in many specialities and in general practice can expect to encounter it. Most tremors can be classified on the basis of four observable clinical characteristics: anatomical pattern; the relative prominence of the tremor at rest, on maintaining a posture, and with action; tremor frequency; and tremor amplitude. A resting tremor suggests Parkinson's disease, and the diagnosis then depends on a judgement about whether the patient has other signs of parkinsonism. The most common causes of postural tremor are physiological tremor, essential tremor and drug-induced tremor. The differential diagnosis may also include dystonic tremor and psychogenic tremor, while metabolic tremor caused by thyrotoxicosis should be considered in any recent-onset postural tremor. Wilson's disease and fragile X-associated tremor/ataxia syndrome are rarer conditions that may present with tremor and are very important to identify. There is a small but genuine diagnostic grey zone between Parkinson's disease and more benign tremor disorders such as essential tremor and dystonic tremor, in which resting and postural tremor coexist with mild or equivocal non-tremor parkinsonian signs. The authors review clinical features and investigational techniques that may help to discriminate this group of hard-to-classify tremors.